Mosquitoes act as vectors for a number of viral and protozoal infections in the world. It has been reported that mosquitoes carry diseases that potentially compromise the health of one-eighth of the world's population and impact the health and economy of approximately 300 million people per year.
In addition to clinically significant diseases like malaria and yellow fever, mosquitoes are also implicated in the transmission of many arboviruses, infections with which cause symptoms ranging from nonspecific flu-like illnesses to encephalitis that may result in death. In addition to humans, domesticated animals such as dogs, cats, horses, cattle, sheep, pigs, as well as wild animals and birds may become infected and experience clinical disease as a result of that infection.
Arboviruses that infect humans and other mammals are members of one of three virus families, Togaviridae, Flavividae, and Bunyaviridae, and include the agent responsible for Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), St. Louis Encephalitis (SLE), La Crosse Encephalitis (LCE), and infection caused by Dengue Virus, and West Nile Virus (WNV). Worldwide, other arboviruses of medical importance include viruses responsible for Japanese Encephalitis (JE) and Venezuelan Equine Encephalitis.
WNV has received significant attention in the United States since its outbreak on the East Coast in 1999 and 2000. Since that outbreak, CDC estimates that WNV has been documented in forty-three of the lower forty-eight states including areas as geographically diverse as Alabama, Arkansas, California, Colorado, and North Dakota. From 1999 through 2001, there were 149 cases of WNV human illness reported to the CDC, including 18 deaths (see www.cdc.gov/ncidod/dvbid/westnile/background.htm).
Transmission of WNV is similar to EEE, WEE, SLE viruses and may involve a cycle that includes mosquitoes and birds. Mosquitoes become infected with WNV when they feed on a bird carrying the virus in its blood. Birds act as amplifying hosts for the virus and, ten to fourteen days after initial infection, the virus can be transmitted to another bird, a human, or another animal host when the mosquito injects saliva containing the virus into that host during feeding. At present, the CDC reports that there are 110 species of birds that may act as amplifying hosts for WNV. Additionally, infected birds may facilitate the spread of the disease as birds can fly long distances after becoming infected.
While humans and other animals may become clinically ill after infection with WNV, they are considered to be incidental hosts since they do not develop enough of the virus in the blood to infect other hosts. Arboviruses other than WNV have different amplifying hosts. For example, the amplifying hosts for JE virus are domestic pigs and wild birds (www.cdc.gov/nicidod/dvbid/jecephalitis/qa.htm), while the amplifying hosts for the virus that causes La Crosse encephalitis are chipmunks and tree squirrels (www.cdc.gov/nicod/dsbid/arbor/ardet.htm).
Another emerging mosquito-borne disease of veterinary importance is heartworm disease, caused by infection with Dirofilaria immitis, and characterized by several developmental stages. Specifically, microfilariae are deposited by female heartworms into the bloodstream of a definitive host—primarily canines, but also felines and ferrets. Once ingested by a mosquito during feeding, the microfilariae develop into infective larvae which, when transmitted to the definitive host, migrate to heart where maturation into adult worms occurs. A number of drug treatments have been developed to treat heartworm. For example, U.S. Pat. No. 5,550,153 to Kerz discloses the use of Ivermectin for treating Dirofilaria immitis infection in canines.
Other research has been directed to the control of heartworm and other arthropod-borne diseases by interfering with transmission cycles. For example, the most common method for controlling mosquitoes that transmit harmful viruses or other microorganisms involves spraying insecticides into areas where the mosquitoes breed. This approach is not without risk, however. For example, the use of insecticides may have a harmful environmental impact, especially to the wetland areas where mosquitos often reside (see, e.g., US 2002/021045 A1). Thus, there is a need for simple, low cost methods to abate arthropod populations, including mosquitos and ticks, and to prevent or impair the transmission of mosquito-borne diseases without widespread environmental damage.
1-N-arylpyrazoles as a class of chemicals are well known in the art, as are methods for their use in controlling parasites including insects, such as fleas or ticks, in mammals, such as domesticated livestock or companion animals, either alone or in combination with other pesticides such as insect growth regulators. See, e.g., EP-A-295,217, EP 295 177, EP-A-840-686, EP-A-352,944, WO 00/35844, WO 98/39972, U.S. Pat. Nos. 5,122,530 5,236,938, 5,232,940, 5,576,429 5,814,652, 5,567,429, 6,090,751 and 6,096,329 as well as Publication No. US 2002-90381-A1. See also copending applications U.S. Ser. Nos. 07/719,942; 08/933,016; 09/174,598; 08/863,182; and 08/863,692. The compounds of the families defined in these patents are extremely active and one of these compounds, 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinylpyrazole, or fipronil, is particularly effective, but not exclusively effective, against fleas and ticks. However, specific results involving the effectiveness of these compounds against mosquitoes generally have not been reported.
Various methods of formulating antiparasitical formulations are known in the art. These include oral formulations, baits, dietary supplements, powders, shampoos, etc. Formulations for localized topical applications of antiparasitical formulations are also known in the art. For example, pour-on solutions comprising 1-N-phenylpyrazole derivatives, such as fipronil, are known in the art and are described in copending application Ser. No. 08/933,016, now U.S. Pat. Nos. 6,010,710, and 6,413,542, issued Jul. 2, 2002 and copending application Ser. No. 10/120,691, filed Apr. 11, 2002 and herein incorporated by reference. Other methods of formulating antiparasitic agents include spot-on formulations.
Spot-on formulations are well known techniques for topically delivering an antiparasitic agent to a limited area of the host. For example, U.S. Pat. No. 5,045,536 describes such formulations for ectoparasites. Other spot-on formulations include U.S. Pat. No. 6,426,333 and copending application U.S. Ser. No. 09/221,470, now allowed, and 10/155,397, filed on May 24, 2002. WO 01/95715 describes a method for controlling ectoparasites in small rodents as well as interrupting or preventing the diseases caused by arthropods of small rodents, which comprise applying topical formulations, such as spot-on compositions, to the skin, or hair of the rodents. WO 01/95715 further provides an enclosure having one or more peripheral openings, which allows the entry and egress of rodents, and an applicator, which comprises the topical formulation and is arranged to contact a rodent. However, WO 01/95715 does not describe a method for preventing or interrupting the transmission of mosquito-borne diseases, in general, or the transmission of WNV, in particular, by administering a formulation comprising a 1-N-phenylpyrazole to a host, in general, or birds, in particular, thereby affecting a simple, low-cost method to abate mosquito populations and to prevent or impair the transmission of mosquito-borne diseases without widespread environmental damage.
Baits are another method of formulating that is known in the art. For example, U.S. patent application Ser. No. 4,564,631 to Elbert et al. relates to a process of preparing a bait containing Pyrethroids for combating Vermin. However, no methods are known to use a commercially available bird station (for example, see bird stations sold by Wild Bird Station, 2295 NW Broad street Murfreesboro, Tenn. 37129 or visit info@wildbirdstation.com) having baits comprising 1-N-arylpyrazole derivatives and/or an IGR either alone or in combination with a known antiparasitic, antihelmintic or insecticidal agent to prevent or to interrupt the transmission of arthropod- or mosquito-borne diseases by birds or other small mammalian hosts.